Endocrinopathies in Paediatric Iron Deficiency Anaemia: Spectrum, Mechanisms, and Reversibility with Treatment

Abstract

Background: Iron deficiency anaemia (IDA) is a prevalent micronutrient disorder in childhood, with well-recognised haematological effects and increasingly reported endocrine consequences. Objectives: This review synthesised evidence on the spectrum, risk factors and reversibility of endocrine dysfunction associated with paediatric IDA. Methods: PubMed/MEDLINE literature published from January 1999 to December 2024 was reviewed using predefined MeSH and free-text search strategies. Eligible studies included children and adolescents aged 0-18 years with biochemically confirmed IDA and at least one endocrine, growth, pubertal, adrenal or neurodevelopmental outcome. The review followed a systematic-style narrative approach guided by SANRA and PRISMA-ScR principles. Methodological quality was assessed using the Newcastle-Ottawa Scale for observational studies and AMSTAR-2 for systematic reviews. No independent meta-analysis was performed. Results: The search identified more than 480 records; 47 studies met the inclusion criteria and were supplemented by five foundational studies. The evidence base comprised 12 systematic reviews or meta-analyses, 18 cohort or case-control studies, nine cross-sectional studies, five randomised controlled trials and three narrative reviews. Reported endocrine manifestations included impaired growth with reduced growth velocity and suppressed IGF-1, subclinical hypothyroidism related to impaired thyroid peroxidase activity, delayed pubertal progression linked to gonadotrophin-axis suppression, attenuated adrenal reserve in severe IDA, and neurodevelopmental deficits after early-life deficiency. Duration of deficiency, delayed treatment, nutritional co-deficiencies, age at exposure, environmental stressors and genetic susceptibility were identified as relevant modifying factors. Iron supplementation, commonly in the range of 3-6 mg/kg/day for 3-6 months, was associated with improvements in growth, thyroid function, somatotropic-axis activity, adrenal reserve and pubertal parameters. Neurodevelopmental recovery appeared less complete when IDA occurred during infancy. Conclusion: Paediatric IDA is associated with multi-axis endocrine dysfunction, much of which may improve following timely iron repletion. Early diagnosis, appropriate treatment and targeted endocrine assessment are important for reducing potentially persistent sequelae.